A/H1N1 and other viruses affecting cystic fibrosis

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Sir, you have reported 4 cases of influenza A/H1N1 infection in
cystic fibrosis (CF) patients in the UK (Whitaker et al., 2009). There are
few reports about influenza A/H1N1 infections in patients with CF and to
our knowledge no reports on CF patients immunized against influenza A/H1N1
so far. Moreover, France and co-workers (France et al., 2010) published 12
patients with CF and influenza A/H1N1 who suffered from a mild clinical
course and only acute respiratory exacerbation. We report on 3 patients
with mainly pulmonary manifestation of CF and positive nasopharyngeal
swabs for influenza A/H1N1. All were treated with oseltamivir (Tamiflu®)
for 5 days. The variability of clinical course reached from acute mild to
moderately severe. To our knowledge, this is the first case report on
influenza A/H1N1 infection in CF patients with influenza A/H1N1
immunization.

Patient 1 was a 14 year old girl chronically colonized
with
Burkholderia multivorans and Staphylococcus aureus. She was immunized with
Pandemrix® 5 days before she developed cough and low grade temperature
without neither dyspnoea nor wheezing. In addition she received Minocyclin
to protect against her chronic colonisation and Streptococcus pneumoniae.
Infectious parameters stayed normal.

Patient 3 was a 46 year old man chronically colonized with
P.
aeruginosa and MRSA and oxygen dependent at night (1.5 l/min). He
developed a fever up to 39.4°C, productive cough, wheezing, and dyspnoea
(SaO2 90 % under 1.5 l/min of oxygen). He was immunized with Pandemrix® 6
weeks prior to admission. CRP was 48 mg/l, white blood cell count 7.72 G/l
(60 % granulocytes, 27 % lymphocytes, 12 % monocytes). Nasopharyngeal
aspirate also revealed RSV in a small quantity. The patient was
additionally treated with Ciprofloxacin, Polymyxin (i.v.), Linezolid
(p.o.) for 14 days each and Prednisolon (i.v.) which was tapered after 1
week.

We can confirm an acute mild course of influenza A/H1N1
infection for
patient 1. However patient 2 and 3 had moderately severe clinical courses.
Both patients were older and patient 3 was oxygen dependent before the
influenza A/H1N1 infection. Thus, patients with a more advanced state of
pulmonary disease may have a more severe course of influenza A/H1N1.

Patient 2 also had confirmed enterovirus and patient 3 had RSV on
nasopharyngeal aspirate. Influenza A and RSV coinfection does not
significantly increase morbidity in a pediatric hospitalized cohort
(Fuller et al., 2005). Coinfection with enterovirus has not been described
in the literature, yet. In CF respiratory viruses generally have been
shown to cause pulmonary exacerbation and disease progression (Wang et al,
1984). Interestingly, there was no loss of lung function 1 month after
influenza A/H1N1 infection in neither three patients (patient 1 had an
FEV1 of 60 % 6 months before and an FEV1 of 59% 1 month after infection,
patient 2 and 3 had an FEV1 of 39 and 31 %, respectively, both 1 month
before and after infection). 2 of our 3 patients were infected with
influenza A/H1N1 and suffered from acute pulmonary exacerbations despite
having been vaccinated. According to the data of Wang (Wang et al 1984)
symptomatic viral infection in CF correlates with deterioration of lung
function. This is in contrast to our data, where lung function fully
recovered. We speculate that the recovery of lung function can be
attributed to consequent early treatment with oseltamivir.

In conclusion, our data provide evidence that influenza A/H1N1 can
cause a more severe clinical course in CF patients with advanced pulmonary
disease. However, our patients only had an acute respiratory exacerbation
and fully recovered after influenza A/H1N1 infection possibly due to
consequent early treatment with oseltamivir.

Furthermore, we speculate that earlier availability of the influenza
A/H1N1 vaccine may have prevented the infection in patient 1 and
alleviated the clinical course in patient 2, however, it did not prevent
disease in patient 3 who was adequately vaccinated.